Advertisement

Dermatologic Side Effects of Systemic Targeted Anticancer Therapy

  • Caroline Robert
  • Christina Mateus
  • Alexander M. M. Eggermont
Chapter

Abstract

Skin, hair, and nails are almost always modified by systemic cancer therapies. These changes can sometimes result in severe adverse events, but most of the patients present with light and moderate skin side effects. Nevertheless, these dermatologic manifestations can significantly impact patients’ quality of life, especially in the case of new targeted agents that are sometimes prescribed continuously over long periods of time.

Patients have to be informed in advance about the skin symptoms that might occur during the course of their treatments. Preventive and symptomatic measures can be advised or prescribed that might optimize treatment compliance and improve quality of life.

Close interaction between oncologists and dermatologist is warranted in order to describe, characterize, and manage the numerous and sometimes new and original skin manifestations of new cancer therapies. In this chapter, we will focus on the side effects associated with targeted anticancer agents since oncologists and physicians are less informed about this field than they are about skin side effects of classical chemotherapeutic agents.

Keywords

Cancer treatment Skin adverse events Targeted agents Hand-foot skin reaction Folliculitis Keratoacanthomas Skin squamous cell carcinoma Hair changes paronychia 

References

  1. 1.
    Robert C, Soria J-C, Spatz A, Le Cesne A, Malka D, Pautier P, et al. Cutaneous side-effects of kinase inhibitors and blocking antibodies. Lancet Oncol. 2005;6(7):491–500.PubMedCrossRefPubMedCentralGoogle Scholar
  2. 2.
    Lacouture ME, Maitland ML, Segaert S, Setser A, Baran R, Fox LP, Epstein JB, Barasch A, Einhorn L, Wagner L, West DP, Rapoport BL, Kris MG, Basch E, Eaby B, Kurtin S, Olsen EA, Chen A, Dancey JE, Trotti A. A proposed EGFR inhibitor dermatologic adverse event-specific grading scale from the MASCC skin toxicity study group. Support Care Cancer. 2010;18:509–22.  https://doi.org/10.1007/s00520-009-0744-x.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Agero ALC, Dusza SW, Benvenuto-Andrade C, Busam KJ, Myskowski P, Halpern AC. Dermatologic side effects associated with the epidermal growth factor receptor inhibitors. J Am Acad Dermatol. 2006;55(4):657–70.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Osio A, Mateus C, Soria J-C, Massard C, Malka D, Boige V, et al. Cutaneous side-effects in patients on long-term treatment with epidermal growth factor receptor inhibitors. Br J Dermatol. 2009;161(3):515–21.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Laux I, Jain A, Singh S, Agus DB. Epidermal growth factor receptor dimerization status determines skin toxicity to HER-kinase targeted therapies. Br J Cancer. 2006;94(1):85–92.PubMedPubMedCentralCrossRefGoogle Scholar
  6. 6.
    Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006;6(10):803–12.PubMedPubMedCentralCrossRefGoogle Scholar
  7. 7.
    Surguladze D, Deevi D, Claros N, Corcoran E, Wang S, Plym MJ, et al. Tumor necrosis factor-alpha and interleukin-1 antagonists alleviate inflammatory skin changes associated with epidermal growth factor receptor antibody therapy in mice. Cancer Res. 2009;69(14):5643–7.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Pérez-Soler R. Can rash associated with HER1/EGFR inhibition be used as a marker of treatment outcome? Oncology (Williston Park). 2003;17(11 Suppl 12):23–8.Google Scholar
  9. 9.
    Amador ML, Oppenheimer D, Perea S, Maitra A, Cusatis G, Cusati G, et al. An epidermal growth factor receptor intron 1 polymorphism mediates response to epidermal growth factor receptor inhibitors. Cancer Res. 2004;64(24):9139–43.PubMedCrossRefPubMedCentralGoogle Scholar
  10. 10.
    Lacouture ME. Insights into the pathophysiology and management of dermatologic toxicities to EGFR-targeted therapies in colorectal cancer. Cancer Nurs. 2007;30(4 Suppl 1):S17–26.PubMedCrossRefPubMedCentralGoogle Scholar
  11. 11.
    Janus N, Launay-Vacher V, Robert C, Souquet P-J, Mateus C, Dreno B, et al. Description of erlotinib-related skin effects management in France. Results of the PRECEDE study. Cancer Radiother. 2009;13(2):97–102.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Akman A, Yilmaz E, Mutlu H, Ozdogan M. Complete remission of psoriasis following bevacizumab therapy for colon cancer. Clin Exp Dermatol. 2009;34(5):e202–4.PubMedCrossRefPubMedCentralGoogle Scholar
  13. 13.
    Lacouture ME, Anadkat MJ, Bensadoun R-J, Bryce J, Chan A, Epstein JB, Eaby-Sandy B, Murphy BA, MASCC Skin Toxicity Study Group. Clinical practice guidelines for the prevention and treatment of EGFR inhibitor-associated dermatologic toxicities. Support Care Cancer. 2011;19:1079–95.  https://doi.org/10.1007/s00520-011-1197-6.CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Jacot W, Bessis D, Jorda E, Ychou M, Fabbro M, Pujol J-L, et al. Acneiform eruption induced by epidermal growth factor receptor inhibitors in patients with solid tumours. Br J Dermatol. 2004;151(1):238–41.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Scope A, Agero ALC, Dusza SW, Myskowski PL, Lieb JA, Saltz L, et al. Randomized double-blind trial of prophylactic oral minocycline and topical tazarotene for cetuximab-associated acne-like eruption. J Clin Oncol. 2007;25(34):5390–6.PubMedCrossRefPubMedCentralGoogle Scholar
  16. 16.
    Jatoi A, Rowland K, Sloan JA, Gross HM, Fishkin PA, Kahanic SP, et al. Tetracycline to prevent epidermal growth factor receptor inhibitor-induced skin rashes: results of a placebo-controlled trial from the North Central Cancer Treatment Group (N03CB). Cancer. 2008;113(4):847–53.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Lacouture ME. The growing importance of skin toxicity in EGFR inhibitor therapy. Oncology (Williston Park). 2009;23(2):194–6.Google Scholar
  18. 18.
    Kerob D, Dupuy A, Reygagne P, Levy A, Morel P, Bernard BA, et al. Facial hypertrichosis induced by Cetuximab, an anti-EGFR monoclonal antibody. Arch Dermatol. 2006;142(12):1656–7.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Ellis LM, Hicklin DJ. VEGF-targeted therapy: mechanisms of anti-tumour activity. Nat Rev Cancer. 2008;8(8):579–91.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Breccia M, Carmosino I, Russo E, Morano SG, Latagliata R, Alimena G. Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib. Eur J Haematol. 2005;74(2):121–3.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Valeyrie L, Bastuji-Garin S, Revuz J, Bachot N, Wechsler J, Berthaud P, et al. Adverse cutaneous reactions to imatinib (STI571) in Philadelphia chromosome-positive leukemias: a prospective study of 54 patients. J Am Acad Dermatol. 2003;48(2):201–6.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Basso FG, Boer CC, Corrêa MEP, Torrezan M, Cintra ML, de Magalhães MHCG, et al. Skin and oral lesions associated to imatinib mesylate therapy. Support Care Cancer. 2009;17(4):465–8.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Brouard M, Saurat JH. Cutaneous reactions to STI571. N Engl J Med. 2001;345(8):618–9.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, et al. Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med. 2002;346(9):645–52.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Deininger MWN, O’Brien SG, Ford JM, Druker BJ. Practical management of patients with chronic myeloid leukemia receiving imatinib. J Clin Oncol. 2003;21(8):1637–47.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Scheinfeld N. Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. J Drugs Dermatol. 2006;5(3):228–31.PubMedPubMedCentralGoogle Scholar
  27. 27.
    Hensley ML, Ford JM. Imatinib treatment: specific issues related to safety, fertility, and pregnancy. Semin Hematol. 2003;40(2 Suppl 2):21–5.PubMedCrossRefPubMedCentralGoogle Scholar
  28. 28.
    Hsiao L-T, Chung H-M, Lin J-T, Chiou T-J, Liu J-H, Fan FS, et al. Stevens-Johnson syndrome after treatment with STI571: a case report. Br J Haematol. 2002;117(3):620–2.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Severino G, Chillotti C, De Lisa R, Del Zompo M, Ardau R. Adverse reactions during imatinib and lansoprazole treatment in gastrointestinal stromal tumors. Ann Pharmacother. 2005;39(1):162–4.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Vidal D, Puig L, Sureda A, Alomar A. Sti571-induced Stevens-Johnson syndrome. Br J Haematol. 2002;119(1):274–5.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Pavithran K, Thomas M. Imatinib induced Stevens-Johnson syndrome: lack of recurrence following re-challenge with a lower dose. Indian J Dermatol Venereol Leprol. 2005;71(4):288–9.PubMedCrossRefPubMedCentralGoogle Scholar
  32. 32.
    Sanchez-Gonzalez B, Pascual-Ramirez JC, Fernandez-Abellan P, Belinchon-Romero I, Rivas C, Vegara-Aguilera G. Severe skin reaction to imatinib in a case of Philadelphia-positive acute lymphoblastic leukemia. Blood. 2003;101(6):2446.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Mahapatra M, Mishra P, Kumar R. Imatinib-induced Stevens-Johnson syndrome: recurrence after re-challenge with a lower dose. Ann Hematol. 2007;86(7):537–8.PubMedCrossRefPubMedCentralGoogle Scholar
  34. 34.
    Brouard MC, Prins C, Mach-Pascual S, Saurat JH. Acute generalized exanthematous pustulosis associated with STI571 in a patient with chronic myeloid leukemia. Dermatology. 2001;203(1):57–9.PubMedCrossRefPubMedCentralGoogle Scholar
  35. 35.
    Schwarz M, Kreuzer K-A, Baskaynak G, Dörken B, le Coutre P. Imatinib-induced acute generalized exanthematous pustulosis (AGEP) in two patients with chronic myeloid leukemia. Eur J Haematol. 2002;69(4):254–6.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Le Nouail P, Viseux V, Chaby G, Billet A, Denoeux JP, Lok C. Drug reaction with eosinophilia and systemic symptoms (DRESS) following imatinib therapy. Ann Dermatol Venereol. 2006;133(8–9 Pt 1):686–8.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Kantarjian H, Giles F, Wunderle L, Bhalla K, O’Brien S, Wassmann B, et al. Nilotinib in imatinib-resistant CML and Philadelphia chromosome-positive ALL. N Engl J Med. 2006;354(24):2542–51.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Kantarjian HM, Giles F, Gattermann N, Bhalla K, Alimena G, Palandri F, et al. Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood. 2007;110(10):3540–6.PubMedCrossRefPubMedCentralGoogle Scholar
  39. 39.
    Woo SM, Huh CH, Park KC, Youn SW. Exacerbation of psoriasis in a chronic myelogenous leukemia patient treated with imatinib. J Dermatol. 2007;34(10):724–6.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Brazzelli V, Prestinari F, Roveda E, Barbagallo T, Bellani E, Vassallo C, et al. Pityriasis rosea-like eruption during treatment with imatinib mesylate: description of 3 cases. J Am Acad Dermatol. 2005;53(5 Suppl 1):S240–3.PubMedCrossRefPubMedCentralGoogle Scholar
  41. 41.
    Konstantopoulos K, Papadogianni A, Dimopoulou M, Kourelis C, Meletis J. Pityriasis rosea associated with imatinib (STI571, Gleevec). Dermatology. 2002;205(2):172–3.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Deguchi N, Kawamura T, Shimizu A, Kitamura R, Yanagi M, Shibagaki N, et al. Imatinib mesylate causes palmoplantar hyperkeratosis and nail dystrophy in three patients with chronic myeloid leukemia. Br J Dermatol. 2006;154(6):1216–8.PubMedPubMedCentralGoogle Scholar
  43. 43.
    Kuraishi N, Nagai Y, Hasegawa M, Ishikawa O. Lichenoid drug eruption with palmoplantar hyperkeratosis due to imatinib mesylate: a case report and a review of the literature. Acta Derm Venereol. 2010;90(1):73–6.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Gómez Fernández C, Sendagorta Cudós E, Casado Verrier B, Feito Rodríguez M, Suárez Aguado J, Vidaurrázaga Díazde Arcaya C. Oral lichenoid eruption associated with imatinib treatment. Eur J Dermatol. 2010;20(1):127–8.PubMedPubMedCentralGoogle Scholar
  45. 45.
    Kawakami T, Kawanabe T, Soma Y. Cutaneous lichenoid eruption caused by imatinib mesylate in a Japanese patient with chronic myeloid leukaemia. Acta Derm Venereol. 2009;89(3):325–6.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Sendagorta E, Herranz P, Feito M, Ramírez P, Feltes R, Floristán U, et al. Lichenoid drug eruption related to imatinib: report of a new case and review of the literature. Clin Exp Dermatol. 2009;34(7):e315–6.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Dalmau J, Peramiquel L, Puig L, Fernández-Figueras MT, Roé E, Alomar A. Imatinib-associated lichenoid eruption: acitretin treatment allows maintained antineoplastic effect. Br J Dermatol. 2006;154(6):1213–6.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Prabhash K, Doval DC. Lichenoid eruption due to imatinib. Indian J Dermatol Venereol Leprol. 2005;71(4):287–8.PubMedCrossRefPubMedCentralGoogle Scholar
  49. 49.
    Ena P, Chiarolini F, Siddi GM, Cossu A. Oral lichenoid eruption secondary to imatinib (Glivec). J Dermatolog Treat. 2004;15(4):253–5.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Arora B, Kumar L, Sharma A, Wadhwa J, Kochupillai V. Pigmentary changes in chronic myeloid leukemia patients treated with imatinib mesylate. Ann Oncol. 2004;15(2):358–9.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Tsao AS, Kantarjian H, Cortes J, O’Brien S, Talpaz M. Imatinib mesylate causes hypopigmentation in the skin. Cancer. 2003;98(11):2483–7.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Etienne G, Cony-Makhoul P, Mahon F-X. Imatinib mesylate and gray hair. N Engl J Med. 2002;347(6):446.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Mcpherson T, Sherman V, Turner R. Imatinib-associated hyperpigmentation, a side effect that should be recognized. J Eur Acad Dermatol Venereol. 2009;23(1):82–3.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Dippel E, Haas N, Grabbe J, Schadendorf D, Hamann K, Czarnetzki BM. Expression of the c-kit receptor in hypomelanosis: a comparative study between piebaldism, naevus depigmentosus and vitiligo. Br J Dermatol. 1995;132(2):182–9.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Cario-André M, Ardilouze L, Pain C, Gauthier Y, Mahon F-X, Taieb A. Imatinib mesilate inhibits melanogenesis in vitro. Br J Dermatol. 2006;155(2):493–4.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Hamm M, Touraud JP, Mannone L, Klisnick J, Ponnelle T, Lambert D. Imatinib-induced purpuric vasculitis. Ann Dermatol Venereol. 2003;130(8–9 Pt 1):765–7.PubMedPubMedCentralGoogle Scholar
  57. 57.
    Clark SH, Duvic M, Prieto VG, Prietol VG. Mycosis fungoides-like reaction in a patient treated with Gleevec. J Cutan Pathol. 2003;30(4):279–81.PubMedCrossRefPubMedCentralGoogle Scholar
  58. 58.
    Rousselot P, Larghero J, Raffoux E, Calvo F, Tulliez M, Giraudier S, et al. Photosensitization in chronic myelogenous leukaemia patients treated with imatinib mesylate. Br J Haematol. 2003;120(6):1091–2.PubMedCrossRefPubMedCentralGoogle Scholar
  59. 59.
    Talpaz M, Shah NP, Kantarjian H, Donato N, Nicoll J, Paquette R, et al. Dasatinib in imatinib-resistant Philadelphia chromosome-positive leukemias. N Engl J Med. 2006;354(24):2531–41.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Hochhaus A, Kantarjian HM, Baccarani M, Lipton JH, Apperley JF, Druker BJ, et al. Dasatinib induces notable hematologic and cytogenetic responses in chronic-phase chronic myeloid leukemia after failure of imatinib therapy. Blood. 2007;109(6):2303–9.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Robert C. Cutaneous side effects of antiangiogenic agents. Bull Cancer. 2007;94 Spec No:S260–4.Google Scholar
  62. 62.
    Robert C, Mateus C, Spatz A, Wechsler J, Escudier B. Dermatologic symptoms associated with the multikinase inhibitor sorafenib. J Am Acad Dermatol. 2009;60(2):299–305.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Abou-Alfa GK, Schwartz L, Ricci S, Amadori D, Santoro A, Figer A, et al. Phase II study of sorafenib in patients with advanced hepatocellular carcinoma. J Clin Oncol. 2006;24(26):4293–300.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Blumenschein GR Jr, Gatzemeier U, Fossella F, Stewart DJ, Cupit L, Cihon F, et al. Phase II, multicenter, uncontrolled trial of single-agent sorafenib in patients with relapsed or refractory, advanced non-small-cell lung cancer. J Clin Oncol. 2009;27(26):4274–80.PubMedCrossRefPubMedCentralGoogle Scholar
  65. 65.
    Cheng A-L, Kang Y-K, Chen Z, Tsao C-J, Qin S, Kim JS, et al. Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol. 2009;10(1):25–34.CrossRefPubMedGoogle Scholar
  66. 66.
    Escudier B, Eisen T, Stadler WM, Szczylik C, Oudard S, Staehler M, et al. Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J Clin Oncol. 2009;27(20):3312–8.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Llovet JM, Di Bisceglie AM, Bruix J, Kramer BS, Lencioni R, Zhu AX, et al. Design and endpoints of clinical trials in hepatocellular carcinoma. J Natl Cancer Inst. 2008;100(10):698–711.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Ratain MJ, Eisen T, Stadler WM, Flaherty KT, Kaye SB, Rosner GL, et al. Phase II placebo-controlled randomized discontinuation trial of sorafenib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2006;24(16):2505–12.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Ryan CW, Goldman BH, Lara PN Jr, Mack PC, Beer TM, Tangen CM, et al. Sorafenib with interferon alfa-2b as first-line treatment of advanced renal carcinoma: a phase II study of the Southwest Oncology Group. J Clin Oncol. 2007;25(22):3296–301.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, Verweij J, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet. 2006;368(9544):1329–38.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Gore ME, Szczylik C, Porta C, Bracarda S, Bjarnason GA, Oudard S, et al. Safety and efficacy of sunitinib for metastatic renal-cell carcinoma: an expanded-access trial. Lancet Oncol. 2009;10(8):757–63.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Rixe O, et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N Engl J Med. 2007;356(2):115–24.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Hurwitz HI, Dowlati A, Saini S, Savage S, Suttle AB, Gibson DM, et al. Phase I trial of pazopanib in patients with advanced cancer. Clin Cancer Res. 2009;15(12):4220–7.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Sternberg CN, Davis ID, Mardiak J, Szczylik C, Lee E, Wagstaff J, et al. Pazopanib in locally advanced or metastatic renal cell carcinoma: results of a randomized phase III trial. J Clin Oncol. 2010;28(6):1061–8.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Hutson TE, Davis ID, Machiels J-PH, De Souza PL, Rottey S, Hong B-F, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J Clin Oncol. 2010;28(3):475–80.PubMedCrossRefPubMedCentralGoogle Scholar
  76. 76.
    Susser WS, Whitaker-Worth DL, Grant-Kels JM. Mucocutaneous reactions to chemotherapy. J Am Acad Dermatol. 1999;40(3):367–98. quiz 399–400.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    von Moos R, Thuerlimann BJK, Aapro M, Rayson D, Harrold K, Sehouli J, et al. Pegylated liposomal doxorubicin-associated hand-foot syndrome: recommendations of an international panel of experts. Eur J Cancer. 2008;44(6):781–90.CrossRefGoogle Scholar
  78. 78.
    Webster-Gandy JD, How C, Harrold K. Palmar-plantar erythrodysesthesia (PPE): a literature review with commentary on experience in a cancer centre. Eur J Oncol Nurs. 2007;11(3):238–46.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Autier J, Escudier B, Wechsler J, Spatz A, Robert C. Prospective study of the cutaneous adverse effects of sorafenib, a novel multikinase inhibitor. Arch Dermatol. 2008;144(7):886–92.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Lipworth AD, Robert C, Zhu AX. Hand-foot syndrome (hand-foot skin reaction, palmar-plantar erythrodysesthesia): focus on sorafenib and sunitinib. Oncology. 2009;77(5):257–71.PubMedCrossRefPubMedCentralGoogle Scholar
  81. 81.
    Autier J, Mateus C, Wechsler J, Spatz A, Robert C. Cutaneous side effects of sorafenib and sunitinib. Ann Dermatol Venereol. 2008;135(2):148–53. quiz 147, 154.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Sibaud V, Dalenc F, Chevreau C, Roché H, Delord J-P, Mourey L, Lacaze J-L, Rahhali N, Taïeb C. HFS-14, a specific quality of life scale developed for patients suffering from hand-foot syndrome. Oncologist. 2011;16:1469–78.  https://doi.org/10.1634/theoncologist.2011-0033.CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Lacouture ME, Reilly LM, Gerami P, Guitart J. Hand foot skin reaction in cancer patients treated with the multikinase inhibitors sorafenib and sunitinib. Ann Oncol. 2008;19(11):1955–61.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Yang C-H, Lin W-C, Chuang C-K, Chang Y-C, Pang S-T, Lin Y-C, et al. Hand-foot skin reaction in patients treated with sorafenib: a clinicopathological study of cutaneous manifestations due to multitargeted kinase inhibitor therapy. Br J Dermatol. 2008;158(3):592–6.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Lacouture ME, Wu S, Robert C, Atkins MB, Kong HH, Guitart J, et al. Evolving strategies for the management of hand-foot skin reaction associated with the multitargeted kinase inhibitors sorafenib and sunitinib. Oncologist. 2008;13(9):1001–11.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Giacchero D, Ramacciotti C, Arnault JP, Brassard M, Baudin E, Maksimovic L, Mateus C, Tomasic G, Wechsler J, Schlumberger M, Robert C. A new spectrum of skin toxic effects associated with the multikinase inhibitor vandetanib. Arch Dermatol. 2012;148:1418–20.  https://doi.org/10.1001/2013.jamadermatol.192.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Robert C, Faivre S, Raymond E, Armand J-P, Escudier B. Subungual splinter hemorrhages: a clinical window to inhibition of vascular endothelial growth factor receptors? Ann Intern Med. 2005;143(4):313–4.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Lee WJ, Lee JL, Chang SE, Lee MW, Kang YK, Choi JH, et al. Cutaneous adverse effects in patients treated with the multitargeted kinase inhibitors sorafenib and sunitinib. Br J Dermatol. 2009;161(5):1045–51.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Motzer RJ, Hutson TE, Tomczak P, Michaelson MD, Bukowski RM, Oudard S, et al. Overall survival and updated results for sunitinib compared with interferon alfa in patients with metastatic renal cell carcinoma. J Clin Oncol. 2009;27(22):3584–90.PubMedPubMedCentralCrossRefGoogle Scholar
  90. 90.
    Kong HH, Turner ML. Array of cutaneous adverse effects associated with sorafenib. J Am Acad Dermatol. 2009;61(2):360–1.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    MacGregor JL, Silvers DN, Grossman ME, Sherman WH. Sorafenib-induced erythema multiforme. J Am Acad Dermatol. 2007;56(3):527–8.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Kong HH, Sibaud V, Chanco Turner ML, Fojo T, Hornyak TJ, Chevreau C. Sorafenib-induced eruptive melanocytic lesions. Arch Dermatol. 2008;144(6):820–2.PubMedPubMedCentralCrossRefGoogle Scholar
  93. 93.
    Rosenbaum SE, Wu S, Newman MA, West DP, Kuzel T, Lacouture ME. Dermatological reactions to the multitargeted tyrosine kinase inhibitor sunitinib. Support Care Cancer. 2008;16(6):557–66.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Robert C, Spatz A, Faivre S, Armand J-P, Raymond E. Tyrosine kinase inhibition and grey hair. Lancet. 2003;361(9362):1056.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Hartmann JT, Kanz L. Sunitinib and periodic hair depigmentation due to temporary c-KIT inhibition. Arch Dermatol. 2008;144(11):1525–6.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Billemont B, Barete S, Rixe O. Scrotal cutaneous side effects of sunitinib. N Engl J Med. 2008;359(9):975–6. discussion 976.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Suwattee P, Chow S, Berg BC, Warshaw EM. Sunitinib: a cause of bullous palmoplantar erythrodysesthesia, periungual erythema, and mucositis. Arch Dermatol. 2008;144(1):123–5.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Guevremont C, Alasker A, Karakiewicz PI. Management of sorafenib, sunitinib, and temsirolimus toxicity in metastatic renal cell carcinoma. Curr Opin Support Palliat Care. 2009;3(3):170–9.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Bennani-Lahlou M, Mateus C, Escudier B, Massard C, Soria J-C, Spatz A, et al. Eruptive nevi associated with sorafenib treatment. Ann Dermatol Venereol. 2008;135(10):672–4.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Dhomen N, Reis-Filho JS, da Rocha Dias S, Hayward R, Savage K, Delmas V, et al. Oncogenic Braf induces melanocyte senescence and melanoma in mice. Cancer Cell. 2009;15(4):294–303.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Wajapeyee N, Serra RW, Zhu X, Mahalingam M, Green MR. Oncogenic BRAF induces senescence and apoptosis through pathways mediated by the secreted protein IGFBP7. Cell. 2008;132(3):363–74.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Arnault JP, Wechsler J, Escudier B, Spatz A, Tomasic G, Sibaud V, et al. Keratoacanthomas and squamous cell carcinomas in patients receiving sorafenib. J Clin Oncol. 2009;27(23):e59–61.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Kwon EJ, Kish LS, Jaworsky C. The histologic spectrum of epithelial neoplasms induced by sorafenib. J Am Acad Dermatol. 2009;61(3):522–7.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Clausen OPF, Aass HCD, Beigi M, Purdie KJ, Proby CM, Brown VL, et al. Are keratoacanthomas variants of squamous cell carcinomas? A comparison of chromosomal aberrations by comparative genomic hybridization. J Invest Dermatol. 2006;126(10):2308–15.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Cribier B, Asch P, Grosshans E. Differentiating squamous cell carcinoma from keratoacanthoma using histopathological criteria. Is it possible? A study of 296 cases. Dermatology. 1999;199(3):208–12.PubMedCrossRefPubMedCentralGoogle Scholar
  106. 106.
    Hodak E, Jones RE, Ackerman AB. Solitary keratoacanthoma is a squamous-cell carcinoma: three examples with metastases. Am J Dermatopathol. 1993;15(4):332–42. discussion 343–52.PubMedCrossRefPubMedCentralGoogle Scholar
  107. 107.
    Robinson MJ, Cobb MH. Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 1997;9(2):180–6.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Dhomen N, Marais R. BRAF signaling and targeted therapies in melanoma. Hematol Oncol Clin North Am. 2009;23(3):529–45. ix.PubMedCrossRefPubMedCentralGoogle Scholar
  109. 109.
    Heidorn SJ, Milagre C, Whittaker S, Nourry A, Niculescu-Duvas I, Dhomen N, et al. Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF. Cell. 2010;140(2):209–21.PubMedPubMedCentralCrossRefGoogle Scholar
  110. 110.
    Mateus C, Robert C. New drugs in oncology and skin toxicity. Rev Med Interne. 2009;30(5):401–10.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Poulikakos PI, Zhang C, Bollag G, Shokat KM, Rosen N. RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF. Nature. 2010;464(7287):427–30.PubMedPubMedCentralCrossRefGoogle Scholar
  112. 112.
    Arnault J-P, Mateus C, Escudier B, Tomasic G, Wechsler J, Hollville E, et al. Skin tumors induced by sorafenib; paradoxical RAS-RAF pathway activation and oncogenic mutations of HRAS, TP53 and TGFBR1. Clin Cancer Res. 2012;18(1):263–72. Epub 2011 Nov 17. Available de: http://www.ncbi.nlm.nih.gov/pubmed/22096025. Cité 2011 Dec 18.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Robert C, Arnault J-P, Mateus C. RAF inhibition and induction of cutaneous squamous cell carcinoma. Curr Opin Oncol. 2011;23(2):177–82.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Long GV, Trefzer U, Davies MA, Kefford RF, Ascierto PA, Chapman PB, Puzanov I, Hauschild A, Robert C, Algazi A, Mortier L, Tawbi H, Wilhelm T, Zimmer L, Switzky J, Swann S, Martin A-M, Guckert M, Goodman V, Streit M, Kirkwood JM, Schadendorf D. Dabrafenib in patients with Val600Glu or Val600Lys BRAF-mutant melanoma metastatic to the brain (BREAK-MB): a multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13:1087–95.  https://doi.org/10.1016/S1470-2045(12)70431-X.CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Robert C, Karaszewska B, Schachter J, Rutkowski P, Mackiewicz A, Stroiakovski D, Lichinitser M, Dummer R, Grange F, Mortier L, Chiarion-Sileni V, Drucis K, Krajsova I, Hauschild A, Lorigan P, Wolter P, Long GV, Flaherty K, Nathan P, Ribas A, Martin A-M, Sun P, Crist W, Legos J, Rubin SD, Little SM, Schadendorf D. Improved overall survival in melanoma with combined dabrafenib and trametinib. N Engl J Med. 2015;372:30–9.  https://doi.org/10.1056/NEJMoa1412690.CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Ellard SL, Clemons M, Gelmon KA, Norris B, Kennecke H, Chia S, et al. Randomized phase II study comparing two schedules of everolimus in patients with recurrent/metastatic breast cancer: NCIC Clinical Trials Group IND.163. J Clin Oncol. 2009;27(27):4536–41.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Chapman PB, Hauschild A, Robert C, Larkin J, Haanen JB, Ribas A, Hoog D. Updated overall survival (OS) results for BRIM-3, a phase III randomized, open-label, multicenter trial comparing BRAF inhibitor vemurafenib (vem) with dacarbazine (DTIC) in previously untreated patients with BRAFV600E-mutated melanoma. J Clin Oncol. 2012;30:Suppl.8502.abstract.Google Scholar
  118. 118.
    Hauschild A, Grob J-J, Demidov LV, Jouary T, Gutzmer R, Millward M, Rutkowski P, Blank CU, Miller WH Jr, Kaempgen E, Martín-Algarra S, Karaszewska B, Mauch C, Chiarion-Sileni V, Martin A-M, Swann S, Haney P, Mirakhur B, Guckert ME, Goodman V, Chapman PB. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380:358–65.  https://doi.org/10.1016/S0140-6736(12)60868-X.CrossRefPubMedPubMedCentralGoogle Scholar
  119. 119.
    Boussemart L, Girault I, Malka-Mahieu H, Mateus C, Routier E, Rubington M, Kamsu-Kom N, Thomas M, Tomasic G, Agoussi S, Breckler M, Laporte M, Lacroix L, Eggermont AM, Cavalcanti A, Grange F, Adam J, Vagner S, Robert C. Secondary tumors arising in patients undergoing BRAF inhibitor therapy exhibit increased BRAF-CRAF heterodimerization. Cancer Res. 2016;76:1476–84.  https://doi.org/10.1158/0008-5472.CAN-15-2900-T.CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    O’Donnell A, Faivre S, Burris HA 3rd, Rea D, Papadimitrakopoulou V, Shand N, et al. Phase I pharmacokinetic and pharmacodynamic study of the oral mammalian target of rapamycin inhibitor everolimus in patients with advanced solid tumors. J Clin Oncol. 2008;26(10):1588–95.PubMedCrossRefPubMedCentralGoogle Scholar
  121. 121.
    Boussemart L, Boivin C, Claveau J, Tao YG, Tomasic G, Routier E, Mateus C, Deutsch E, Robert C. Vemurafenib and Radiosensitization. JAMA Dermatol. 2013;149(7):855–7.  https://doi.org/10.1001/jamadermatol.2013.4200.CrossRefPubMedPubMedCentralGoogle Scholar
  122. 122.
    Boussemart L, Routier E, Mateus C, Opletalova K, Sebille G, Kamsu-Kom N, Thomas M, Vagner S, Favre M, Tomasic G, Wechsler J, Lacroix L, Robert C. Prospective study of cutaneous side-effects associated with the BRAF inhibitor vemurafenib: a study of 42 patients. Ann Oncol. 2013;24:1691–7.  https://doi.org/10.1093/annonc/mdt015.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Schad K, Baumann Conzett K, Zipser MC, Enderlin V, Kamarashev J, French LE, Dummer R. Mitogen-activated protein/extracellular signal-regulated kinase kinase inhibition results in biphasic alteration of epidermal homeostasis with keratinocytic apoptosis and pigmentation disorders. Clin Cancer Res. 2010;16:1058–64.  https://doi.org/10.1158/1078-0432.CCR-09-1766.CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Long GV, Stroyakovskiy D, Gogas H, Levchenko E, de Braud F, Larkin J, Garbe C, Jouary T, Hauschild A, Grob JJ, Chiarion Sileni V, Lebbe C, Mandalà M, Millward M, Arance A, Bondarenko I, Haanen JBAG, Hansson J, Utikal J, Ferraresi V, Kovalenko N, Mohr P, Probachai V, Schadendorf D, Nathan P, Robert C, Ribas A, DeMarini DJ, Irani JG, Casey M, Ouellet D, Martin A-M, Le N, Patel K, Flaherty K. Combined BRAF and MEK inhibition versus BRAF inhibition alone in melanoma. N Engl J Med. 2014;371:1877–88.  https://doi.org/10.1056/NEJMoa1406037.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Motzer RJ, Escudier B, Oudard S, Hutson TE, Porta C, Bracarda S, et al. Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomised, placebo-controlled phase III trial. Lancet. 2008;372(9637):449–56.PubMedCrossRefPubMedCentralGoogle Scholar
  126. 126.
    Tabernero J, Rojo F, Calvo E, Burris H, Judson I, Hazell K, et al. Dose- and schedule-dependent inhibition of the mammalian target of rapamycin pathway with everolimus: a phase I tumor pharmacodynamic study in patients with advanced solid tumors. J Clin Oncol. 2008;26(10):1603–10.PubMedCrossRefPubMedCentralGoogle Scholar
  127. 127.
    Punt CJA, Boni J, Bruntsch U, Peters M, Thielert C. Phase I and pharmacokinetic study of CCI-779, a novel cytostatic cell-cycle inhibitor, in combination with 5-fluorouracil and leucovorin in patients with advanced solid tumors. Ann Oncol. 2003;14(6):931–7.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Raymond E, Alexandre J, Faivre S, Vera K, Materman E, Boni J, et al. Safety and pharmacokinetics of escalated doses of weekly intravenous infusion of CCI-779, a novel mTOR inhibitor, in patients with cancer. J Clin Oncol. 2004;22(12):2336–47.PubMedCrossRefPubMedCentralGoogle Scholar
  129. 129.
    Bjelogrlić SK, Srdić T, Radulović S. Mammalian target of rapamycin is a promising target for novel therapeutic strategy against cancer. J BUON. 2006;11(3):267–76.PubMedPubMedCentralGoogle Scholar
  130. 130.
    Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998;31(5):335–40.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Nguyen A, Hoang V, Laquer V, Kelly KM. Angiogenesis in cutaneous disease: part I. J Am Acad Dermatol. 2009;61(6):921–42. quiz 943–4.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Amato RJ, Jac J, Giessinger S, Saxena S, Willis JP. A phase 2 study with a daily regimen of the oral mTOR inhibitor RAD001 (everolimus) in patients with metastatic clear cell renal cell cancer. Cancer. 2009;115(11):2438–46.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Atkins MB, Hidalgo M, Stadler WM, Logan TF, Dutcher JP, Hudes GR, et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004;22(5):909–18.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Atkins MB, Yasothan U, Kirkpatrick P. Everolimus. Nat Rev Drug Discov. 2009;8(7):535–6.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Caroline Robert
    • 1
    • 2
    • 3
  • Christina Mateus
    • 1
    • 2
    • 3
  • Alexander M. M. Eggermont
    • 1
    • 2
    • 3
  1. 1.Department of Dermatology and U INSERM U981Institute Gustave RoussyVillejuifFrance
  2. 2.Department of DermatologyInstitute Gustave RoussyVillejuifFrance
  3. 3.Department of Surgical and Medical OncologyInstitut de Cancérologie Gustave RoussyVillejuif-ParisFrance

Personalised recommendations